MX2011005512A

MX2011005512A - Process for the production of an n-butyric acid compound in micro encapsulated form, for animal or human consumption.

Info

Publication number: MX2011005512A
Application number: MX2011005512A
Authority: MX
Inventors: Maurizio Lorenzon
Original assignee: Sila S R L
Priority date: 2008-11-28
Filing date: 2009-11-25
Publication date: 2011-06-16
Also published as: BRPI0916468B1; EP2352386B1; US8603538B2; SI2352386T1; CA2744350C; CN102227171A; US20110287104A1; WO2010060914A1; PL2352386T3; RU2506809C2; CN102227171B; EP2352386A1; IT1392214B1; ITPD20080352A1; ES2396035T3; BRPI0916468A2; CA2744350A1; RU2011126340A

Abstract

A process for the production of an n-butyric acid compound in microencapsulated form comprises the stages of: - providing a granular material based on the n-butyric acid compound, - mixing the granular material with a matrix having a content of long-chain C14-C22 saturated fatty acids of from 40 % to 95 %, and an amount of between 1 % and 20 % of a mineral agent in which an effective amount of calcium sulphate dihydrate is present, heating the mixture to a temperature higher than the melting temperature of the lipid component of the matrix, - spraying the mixture into a cooling chamber having a temperature lower than the melting temperature of the lipid component of the matrix, so that the latter solidifies around the granular material, forming a covering thereof.

Description

PROCESS FOR THE PRODUCTION OF AN N-BUTYRIC ACID COMPOUND IN A MICROENCAPSULATED FORM, FOR ANIMAL CONSUMPTION OR HUMAN FIELD OF THE INVENTION The present invention relates to a process for the production of a n-butyric acid compound in microencapsulated form for animal or human consumption, having the characteristics set forth in the preamble of the main claim.

BACKGROUND OF THE INVENTION It is known that some n-butyric acid compounds have advantageous biological effects on the digestive system, stimulating the growth of intestinal hair and modifying the development of gastro-enteric microorganisms.

Butyric acid is a short-chain monocarboxylic fatty acid (chain of 4 carbon atoms) that is also classified among volatile fatty acids (VFAs) together with acetic acid (chain of 2 carbon atoms) ) and propionic acid (chain of 3 carbon atoms). Butyric acid has 2 isomers, n-butyric acid and isobutyric acid. At room temperature, n-butyric acid is in the liquid form and also has a REF. : 220373 characteristic rancid butter smell that is perceived by humans and by many species of animals even at very low concentrations.

Among the n-butyric acid compounds that are of great interest are their salts and their asters, which are generally referred to as "butyrates", and in particular, their sodium salt.

The n-butyric acid ester is commercially available in the liquid form, while the sodium salt of the n-butyric acid is commercially available both in the liquid form (in 50% aqueous solution - as a direct product of the reaction for the synthesis of the sodium salt of n-butyric acid) and in the granular form (as a white powder that is stable up to 250 ° C).

Depending on the surrounding environment, the n-butyric acid compounds may be in the dissociated form or in the undissociated form; the latter is of particular importance at the biological level, since it can be absorbed by the intestinal walls and cell membranes of microorganisms and may have a more marked effect than the dissociated form.

Butyrates are produced mainly from hydrocarbons (cellulose and starch) by fermentation in anaerobic conditions by several microorganisms and this process is also carried out in the large intestine. After its formation, the butyrate is partially metabolised and the non-metabolized fraction of the butyrate is not Dissociated is absorbed in the large intestine and enters the circulation.

It can be seen from the data reported in the literature that volatile fatty acid salts can inhibit the growth of hemolytic strains of Escherichia coli by up to 50% (Galfi P., Neogrady S., 1992).

Among these salts, the n-butyric acid salts have the greatest inhibitory potency and this increases with the reduction in pH, which favors the presence of their undissociated form. It has become apparent from studies on the effects of a salt of n-butyric acid in several strains of microorganisms of the digestive system (Galfi P., Neogrady S., 1991) that the reduction in the development of E. coli is due to a direct effect of butyrate and an increase in the development of Lactobacillus. Therefore, the antimicrobial affect of this salt is selective. Other microorganisms that are sensitive to n-butyric acid salts and pH are: Clostridium acetobutylicum, Escherichia coli, Streptococcus cremoris, Lactococcus lactis and cremoris and Salmonella species, while Lactobacillus and Streptococcus bovis species are less sensitive.

Butyrate has an additional biological effect, more precisely, a stimulating effect on the growth of the wall of the digestive system (Galfi P., Neogrady S., 1991).

These studies are supported by the results obtained from feeding tests on animals, which show a greater daily increase in weight, improved use of food and reduced mortality.

Along with its considerable capabilities, however, the n-butyric acid compounds have a considerable disadvantage due to the rancid butter odor certainly unpleasant, which characterizes the start-up of n-butyric acid and which complicates the production and storage processes .

In fact, these compounds do not have pleasant odors per se, but are particularly sensitive to acidic environments in which they can easily hydrolyze and re-form the original n-butyric acid, with the disadvantages mentioned above.

For this reason, if the butyrate were administered as such to an animal or a human being, the n-butyric acid would form immediately at the gastric level, no longer making the butyrate available for absorption at the intestinal level. To limit this problem, it is known to microencapsulate the butyrate by coating it with a lipid matrix.

EP1354520, in the name of the Applicant, describes a granulated product having a microencapsulated butyrate center in a lipid structure with buffering compounds, such as carbonates and bicarbonates.

In this way, it is intended to protect the butyrate from any of the acidic compounds present in the diet and, in particular, of the strongly acidic environment that is present at the gastric level, but allow it to be released at the intestinal level, by means of the degrading action of the specific enzymes in the lipid matrix.

Despite the excellence of the principle underlying this measure, however, the problem can be considered that it only partially resolves, given that a considerable fraction of the microencapsulated product is found to be degraded at the gastric level. In addition, the Applicant has also found that, particularly in the case of feed for pigs, some of the butyrate is also hydrolyzed during storage due to the presence of acidic compounds in the feed.

WO 2008/098807, in the name of the Applicant, describes a granulated product having a center of conjugated linoleic acid microencapsulated in a lipid matrix having a structure of mineral agent, comprising silica and optionally calcium carbonate or calcium sulfate dihydrate .

Therefore, there is a need, in the technical field in question, to improve the process for the production of a n-butyric acid compound in the microencapsulated form to improve the final characteristics of the product, in particular its resistance to acidic environments.

DETAILED DESCRIPTION OF THE INVENTION The problem underlying the present invention is to provide a process for the production of a n-butyric acid compound in the microencapsulated form for animal or human consumption, which is functionally designed to overcome the limitations described above with reference to the technique above mentioned.

Within the scope of this problem, an object of the invention is to provide a product which is based on a n-butyric acid compound and which allows a slow and controlled release of the active ingredient in the intestine.

A further objective of the invention is to provide a process that does not increase the production costs of the product.

This problem is solved, and these objects are achieved by the present invention by means of a process for the production of a n-butyric acid compound in the microencapsulated form according to the appended claims.

In general, the process according to the invention follows the microencapsulation process by a spray cooling technique, providing the steps of: provide a granular material based on a n-butyric acid compound, - mixing the granular material with a matrix based on lipid, heating the mixture to a temperature higher than the melting temperature of the matrix, atomizing the mixture obtained in this way in a cooling chamber having a temperature lower than the melting temperature of the matrix, so that the latter solidifies around the granular material, covering it.

In this way, a granular product of appropriate size is obtained, formed by an inner center which is based on a n-butyric acid compound and is surrounded and protected by a lipid-based cover, in other words it is microencapsulated.

Preferably, the compound is a salt or ester of n-butyric acid and, more preferably, is the sodium salt of n-butyric acid.

In a first embodiment, the granular material is based on sodium butyrate in the pulverized form, with a degree of purity greater than 90-95%, having appropriate particle dimensions, for example, between 10 and 200 microns.

In a second preferred embodiment, the granular material is composed of a solid support in the pulverized form, in which an aqueous solution of sodium butyrate is adsorbed.

The adsorption step is carried out by mixing the aqueous solution, typically with a 50% sodium butyrate content, with the solid support in a mixer which is subjected to high speed agitation and maintained at a temperature of about 60-70 ° C. 70 ° C.

The solid support is preferably inorganic to resist the degradation phenomena for a long period of time and, more preferably, is based on silica, with average dimensions between 10 and 80 micrometers, preferably between 15 and 20 micrometers.

The silica used is preferably of synthetic derivation, substantially free of metals, and with a neutral pH, to avoid dissociation of sodium butyrate.

The amount of silica used will be sufficient to achieve complete adsorption of sodium butyrate, generally between 33% and 55% relative to liquid sodium butyrate.

Once this first stage of the process is completed, the pulverized material is obtained, which slides smoothly, which will constitute the interior center of the finished product.

It is important to emphasize that, as well as the adsorption of the liquid sodium butyrate, the silica confers an appropriate consistency in the mixture obtained in a subsequent process step for the entrance to the atomization cooling chamber, to promote the correct formation of the granular product finished.

The granular material obtained in one of the two processes described above, is then mixed with a lipid-based matrix having a content of between 40% and 95% of saturated fatty acids with 14, 16, 18, 20 and 22 carbon atoms. carbon (briefly C14, C16, C18, C20 and C22), in which an amount of between 1% and 20% by weight, relative to the matrix, of a mineral agent is also present.

When the granular material is formed by the sodium butyrate in the pulverized form, the mineral agent is added to the mixture of the lipid and sodium butyrate matrix, whereas if the granular material is formed by an aqueous solution of sodium butyrate adsorbed on silica, the mineral agent is preferably added to the aqueous solution during the adsorption step, together with the silica.

According to a first aspect of the invention, the mineral agent comprises an effective amount of calcium sulfate dihydrate, CaS04.2 (H20).

The fraction of calcium sulfate dihydrate in the mineral agent is preferably greater than 50%; more preferably, it is greater than 95%.

The use of calcium sulfate dihydrate has been found to be essential to obtain a finished product having the optimum characteristics of resistance to acidic environments. In particular, this compound has been found to be much more effective than other mineral agents commonly used in the field, such as, for example, calcium carbonate. In addition, it will be observed that this result is surprising, given that calcium carbonate is a basic salt and, thus, theoretically more appropriate to protect the center of the microencapsulated product in acidic environment.

According to a further aspect of the invention, at least 80% of the weight of the lipid component of the matrix consists of glycerides of saturated C 14 -C 22 fatty acids.

The term "saturated" should not be understood in an absolute sense, but is intended to indicate fatty acids that have a saturation level of at least 99%. Furthermore, it is particularly important that the fatty acids present in the matrix are present substantially in the form of glycerides and not free acids. For this purpose, the percentage of free acids within the lipid component of the matrix should be less than 10% and preferably less than 1%.

Preferably, the glycerides are in the form of triglycerides.

The lipid component of the matrix according to the invention also preferably has a saturated C18 fatty acid content of between 20% and 50% and a C16 saturated fatty acid content of between 50% and 75%, based on to the total saturated fatty acids that constitute the glycerides.

The lipid component of the matrix is preferably based on hydrogenated palm oil.

The composition of the lipid component of the matrix is such that it has a melting point of between 55 ° C and 65 ° C.

The lipid component of the matrix is first heated to the melting point and then mixed with the granular material obtained by the adsorption of the liquid sodium butyrate on the silica, in which the mineral agent may already be present or, alternatively, with the granular material formed by the solid sodium butyrate and the mineral agent.

The mixing is preferably carried out in the presence of suitable emulsifying agents, such as, for example, propylene glycol esters, to promote a homogeneous dispersion of the silica powder or solid sodium butyrate in the lipid matrix.

In addition, other polymeric compounds based on cellulose and / or their derivatives are also preferably added to the mixture as stabilizers, among other things.

The mixing is carried out for about 10-20 minutes to give a homogeneous mixture (although, more precisely, the system obtained can best be defined as a homogeneous suspension of a solid powder in a molten matrix).

According to a variant of the process of the invention, variable amounts between 0.1% and 5% of one or more essential oils, such as flavors, antioxidants and antibacterial agents (strengthening the antibacterial activity of the butyrate itself) may also be added to the mixture.

Examples of the essential oils advantageously used as additives in the mixture described above are oregano oil (for its content of carvacrol and thymol), orange oil (for its content of d-limonene), clove oil or cinnamon oil ( for its content of eugenol) (rosemary oil, garlic oil or sage oil.

Once the desired homogeneity has been reached, the mixture is immediately injected at high pressure and by means of nozzles of the appropriate form, in an atomization cooling chamber in which the temperature is maintained at -2 ° C and -12 ° C, so that, during the short time by which the particles of the mixture remain in air, the lipid component of the matrix can be advantageously solidified according to the per se known procedures (atomization cooling technique).

In this way, a solid, granular product is obtained, comprising an inner center formed by the active ingredient which can be represented by a granule of sodium butyrate or by a silica granule in which the aqueous solution thereof is adsorbed, and a cover coating and protector of the inner center formed by the lipid component of the matrix, the mineral agent and the emulsifying agent.

After atomization, the product is collected in conveyor belts and, when still inside the cooling chamber, subjected to forced ventilation to emerge from the chamber at a temperature lower than the melting point and, thus, in the solid state.

To prevent agglomeration of the granular product, if 80% of its particles have a size smaller than 500 microns, it is sprayed with an anti-agglomeration agent constituted, for example, of silica and / or pearls and / or sepiolites with a size of particle between 75 and 80 micrometers.

The size of the granule depends on the supply pressure and the shape of the nozzle but, if necessary, the product can be sieved to make it consistent with the desired dimensional specification.

By virtue of the specific production process and the matrix used, the obtained cover is arranged continuously and uniformly around the inner butyrate portion.

EXAMPLES OF PREPARATION Example 1 (solid sodium butyrate) 55 g of the lipid matrix constituted by triglycerides of saturated fatty acids C14, C16, C18, to which 10 g of calcium sulphate dihydrate and 5 g of propylene glycol esters had been added, was introduced in a mixer with a heated jacket at a temperature of 70 ° C. The matrix was maintained at a temperature of 70 ° C and 30.6 g of solid sodium butyrate were added thereto in the pulverized form with a degree of purity of 98-99%. The mixture was stirred for approximately 15 minutes to give a homogeneous suspension.

The mixture thus obtained was then supplied to a cooling chamber which was maintained at a temperature of about -10 ° C, in which the mixture was atomized with the use of an appropriate nozzle to obtain granules with an internal center-based of sodium butyrate, covered by a mineral-1-lipid cover.

Example 2 (liquid sodium butyrate - 50% solution) 30 g of a 50% aqueous solution of sodium butyrate, to which 12 g of silica and 7 g of calcium sulfate dihydrate were added, was introduced into a mixer with a jacket heated to a temperature of 70 ° C. The mixture was stirred until the aqueous solution was completely adsorbed, that is, until a smoothly slipping powder was obtained. Then 51 g of C14, C16, C18 saturated fatty acid triglycerides and 1 g of propylene glycol esters were added. The mixture was stirred at a temperature of 65 ° C for about 15 minutes to give a homogeneous suspension.

The mixture in this way obtained after was supplied to a cooling chamber that was maintained at a temperature of about -10 ° C, in which the mixture was atomized with the use of an appropriate nozzle to obtain granules with an inner center formed by a silica granule in which it was adsorbed the solution of aqueous sodium butyrate, covered by a mineral-lipid cover.

Example 3 (solid sodium butyrate - comparative) 70 g of a lipid matrix consisting of triglycerides of saturated fatty acids C14, C16, C18, was introduced in a mixer with a jacket heated to a temperature of 70 ° C. The matrix was maintained at a temperature of 70 ° C and 30 g of solid sodium butyrate in the pulverized form were introduced therein with a degree of purity of 98-99%. The mixture was stirred for approximately 15 minutes to give a homogeneous suspension. The mixture thus obtained was then supplied to a cooling chamber which was maintained at a temperature of about -10 ° C, in which the mixture was atomized with the use of an appropriate nozzle to obtain granules with an internal center-based of sodium butyrate covered by a lipid coating.

Analysis of the products The samples of Examples 1 and 3 were subjected to an in vitro digestion consisting of a series of tests that they reproduce a three stage chemical and enzymatic incubation, according to the test protocol established by Boisen.

For each product to be analyzed, 3-5 g of the sample to be subjected to the digestion test were obtained and weighed, at least in triplicate and with an accuracy of ± 0.1 mg, and were subjected to the three stages described above. continuation .

Each of the three stages tends to reproduce in vitro the different main stages of digestion within the digestive tract (stomach, small intestine and large intestine) with investigation, in particular, of the activity of specific enzymes (lipase) for digestion of the cover of the microcapsules.

Stage 1 The three samples of each microencapsulated product were weighed in 100 mL flasks. 25 were added. mL d phosphate buffer (0.1 M, pH 6.0) to each sample with moderate agitation with a magnetic stirrer. 10 ml of 0.2 M HCl was added to the mixture and the pH was brought to pH 2 with the use of a 1 M HCl or NaOH solution. Then 1 mL of a freshly prepared solution containing 25 mg of pepsin (2000 FIP-U / g) was added to the mixture. The flasks were closed with plastic stoppers and kept in a bath of water at 39 ° C for 2 hours.

Stage 2 10 mL of phosphate buffer (0.2 M, pH 6.8) and 5 mL of a 0.6 M NaOH solution were added to the mixture. The pH was corrected to 6.8 with HCl or NaOH 1. The mixture was stirred moderately with 1 mL of a freshly prepared solution containing 100 mg of pancreatin. After the flasks had been closed with plastic stoppers, the flasks were incubated for 4 hours in a water bath maintained thermostatically at 39 ° C.

Stage 3 The pH of the mixture from the previous step was adjusted to pH 7.0 with the use of a 1 M NaOH solution. Then 100 mg of lipase was added and the mixture was stirred for 18 h at 39 ° C.

Once each of the above steps was completed, a portion of the mixture was extracted and filtered, the residual microcapsules were washed with distilled water and then subjected to the preparation provided by the specific analysis method to identify their content of sodium butyrate.

The content of sodium butyrate was then related to the initial content and reported in the following Table 1.

Table 1 The results provided in Table 1 show that, by virtue of the process according to the invention, the product obtained is more resistant than the reference sample to the acidic environment that is present at the gastric level and, in addition, that the butyrate content of Sodium remains at relatively high levels, greater than the reference sample, favoring the slow release of the active ingredient and allowing its subsequent absorption even at the end, the colon portion of the intestine.

The product obtained can be for human or animal consumption.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. Process for the production of a n-butyric acid compound in the microencapsulated form, comprising the steps of: provide a granular material based on a n-butyric acid compound, - mixing the granular material with a matrix having a C14-C22 saturated long chain fatty acid content of 40% to 95%, heating the mixture to a temperature higher than the melting temperature of the lipid component of the matrix, - atomizing the mixture in a cooling chamber having a temperature lower than the temperature of the lipid component of the matrix, so that the latter solidifies around the granular material, forming a cover for the granular material, characterized in that the matrix comprises a mineral agent in an amount of 1% to 20% relative to the matrix, the mineral agent having a calcium sulfate dihydrate fraction greater than 50%.

2. Process according to claim 1, characterized in that the fraction of the calcium sulfate dihydrate in the mineral agent is greater than 50%, preferably greater than 95%.

3. Process according to claim 1 or 2, characterized in that the long chain C14-C22 saturated fatty acids are in the form of glycerides and represent at least 80% by weight of the matrix.

4. Process according to claim 3, characterized in that the glycerides of saturated fatty acids are derived from hydrogenated palm oil.

5. Process according to any of the preceding claims, characterized in that an effective amount of propylene glycol distearate is provided as an emulsification agent in the matrix.

6. Process according to any of the preceding claims, characterized in that the granular material is formed by adsorbing an aqueous solution of the n-butyric acid compound on a solid support.

7. Process according to claim 6, characterized in that the solid support is based on silica.

8. Process according to claim 6 or 7, characterized in that the mineral agent is added to the aqueous solution during adsorption in the solid support.

9. Process according to any of the preceding claims, characterized in that one or more Essential oils selected from the group consisting of oregano oil, orange oil, clove oil, cinnamon oil, rosemary oil, garlic oil and sage oil are added to the matrix.

10. Process according to any of the preceding claims, characterized in that the compound is the salt of sodium n-butyric acid.

11. Product based on a n-butyric acid compound in the microencapsulated form, characterized in that it is obtained by means of the process according to any of the preceding claims.